We seek to understand the chemical and structural changes which take place in the molecular structure of bone mineral and in its interaction with the organic matrix, from inception through maturation and aging. These changes in bone chemistry influence the quality of bone as a material (mechanical support) and as an ion reservoir (physiological role). The baseline studies of changes in normal bones will be used to assess any effects on bone fabric in various pathological conditions such as osteoporosis, osteopetrosis, ostemalacia, and rickets. To overcome the biological problem of tissue heterogeneity we will fractionate tissue particles according to density and thus prepare material that is more homogeneous with respect to stage of maturation. Fractions ranging from the youngest mineral particles deposited to the most mature mineral will be studied. Furthermore, we will use various animal tissues with known rates of mineral deposition and resorption. Finally we will demineralize or deproteinize the tissue to study separately the mineral and organic components. To overcome the physical problems caused by the small size and multiple impurities of the mineral particles we will use a combination of newly developed techniques to probe the short- and long-range atomic order of these crystallites as well as their relationship with the organic matrix. In addition to classical chemical, crystallographic, electron optic, and spectroscopic analyses, we will use Radial Distribution Functions (RDF), Extended X-Ray Absorption Fine Structure (EXAFS), and Raman microprobe techniques. These analyses will provide a unique description of the main structural chemical and biological events in calcification and aging of bone tissues. We will make full use of the resources and professional personnel in the Connective Tissue Research Group, Mount Sinai Hospital, a group which is actively investigating other aspects of biomineralization using approaches involving anatomical pathology, proteoglycan biochemistry, physical chemistry and x-ray crystallography.